Search PubMed⌕ Search

Biomedical subjects

R C Brown

Publications and source records attributed to R C Brown.

At least 55 records · Page 3Linked to original sources
PubMed1999

Frequent detection of escape from cytotoxic T-lymphocyte recognition in perinatal human immunodeficiency virus (HIV) type 1 transmission: the ariel project for the prevention of transmission of HIV from mother to infant.

Host immunologic factors, including human immunodeficiency virus (HIV)-specific cytotoxic T lymphocytes (CTL), are thought to contribute to the control of HIV type 1 (HIV-1) replication and thus delay disease progression in infected individuals. Host immunologic factors are also likely to influence perinatal transmission of HIV-1 from infected mother to infant. In this study, the potential role of CTL in modulating HIV-1 transmission from mother to infant was examined in 11 HIV-1-infected mothers, 3 of whom transmitted virus to their offspring. Frequencies of HIV-1-specific human leukocyte antigen class I-restricted CTL responses and viral epitope amino acid sequence variation were determined in the mothers and their infected infants. Maternal HIV-1-specific CTL clones were derived from each of the HIV-1-infected pregnant women. Amino acid substitutions within the targeted CTL epitopes were more frequently identified in transmitting mothers than in nontransmitting mothers, and immune escape from CTL recognition was detected in all three transmitting mothers but in only one of eight nontransmitting mothers. The majority of viral sequences obtained from the HIV-1-infected infant blood samples were susceptible to maternal CTL. These findings demonstrate that epitope amino acid sequence variation and escape from CTL recognition occur more frequently in mothers that transmit HIV-1 to their infants than in those who do not. However, the transmitted virus can be a CTL susceptible form, suggesting inadequate in vivo immune control.

Base Sequence↗
PubMed1999

Economic analysis of selected lignocellulose-to-ethanol conversion technologies.

The objective of this case study was to examine the economics of three lignocellulose-to-ethanol conversion technologies: fast pyrolysis integrated with a fermentation step, simultaneous saccharification and fermentation (SSF), and dilute sulfuric acid hydrolysis and fermentation. All technologies were assumed to have an annual production rate of 25 million gallons of ethanol. The three technologies were compared in terms of capital costs, operating costs, and ethanol production costs. Sensitivity analyses were carried out to study the uncertainties of wood costs and ethanol production rates on ethanol production costs. Final economic analysis showed that fast pyrolysis integrated with a fermentation step is comparable with the other two processes and suggests that it should be considered for further development.

Journal Article↗
PubMed1999

Measurements of the effectiveness of dust control on cut-off saws used in the construction industry.

Materials used in the construction industry frequently contain large quantities of silica. When they are cut or shaped with power tools considerable respirable dust can be produced. Three dust control systems for use with cut-off saws have been evaluated on site: wet dust suppression using mains water, the same system using water from a portable water tank, and local exhaust ventilation. The efficiency of water suppression on cut-off saws has been precisely quantified in controlled laboratory conditions by means of measurements with and without dust control. When dust control was used on-site, the mean concentrations of airborne silica were reduced by a factor of between three and seven, the accuracy being limited by the relatively high limit of detection for silica. All controls systems generally reduced respirable dust levels by at least 90%. Although the effectiveness of dust suppression did not depend on blade type, a diamond blade was more effective than a resin-bonded blade with the pressurised water system; cutting a slab with this type of blade could be completed before the water tank required repressurization. In laboratory tests, the application of water reduced the dust concentration to < 4% of its value without control. The method for monitoring the dust concentration was sufficiently sensitive to measure a difference in concentration produced during cutting in different directions. It is important, however, that the pressure in supply reservoirs is properly maintained, that the water is correctly applied and that it is used at the correct rate. If this is done effective dust control can be achieved.

Construction Materials↗
PubMed1998

Protein kinase A stimulates binding of multiple proteins to a U-rich domain in the 3'-untranslated region of lactate dehydrogenase A mRNA that is required for the regulation of mRNA stability.

We have explored the molecular basis of the cAMP-induced stabilization of lactate dehydrogenase A (LDH-A) mRNA and identified four cytoplasmic proteins of 96, 67, 52, and 50 kDa that specifically bind to a 30-nucleotide uridine-rich sequence in the LDH 3'-untranslated region with a predicted stem-loop structure. Mutational analysis revealed that specific protein binding is dependent upon an intact primary nucleotide sequence in the loop as well as integrity of the adjoining double-stranded stem structure, thus indicating a high degree of primary and secondary structure specificity. The critical stem-loop region is located between nucleotides 1473 and 1502 relative to the mRNA cap site and contains a previously identified cAMP-stabilizing region (CSR) required for LDH-A mRNA stability regulation by the protein kinase A pathway. The 3'-untranslated region binding activity of the proteins is up-regulated after protein kinase A activation, whereas protein dephosphorylation is associated with a loss of binding activity. These results imply a cause and effect relationship between LDH-A mRNA stabilization and CSR-phosphoprotein binding activity. We propose that the U-rich CSR is a recognition signal for CSR-binding proteins and for an mRNA processing pathway that specifically stabilizes LDH mRNA in response to activation of the protein kinase A signal transduction pathway.

3' Untranslated Regions↗
PubMed1998

Employment of a phenoxy-substituted acridinium ester as a long-lived chemiluminescent indicator of glucose oxidase activity and its application in an alkaline phosphatase amplification cascade immunoassay.

This paper describes the employment of a novel phenoxy-substituted acridinium ester (di-ortho-bromophenyl-AE) as a chemiluminescent endpoint indicator for ligand binding assays. The reactivity of this compound is such that it is capable of generating a high-intensity chemiluminescent signal at neutral pH. Under these conditions, when present in excess, it has been used as an indicator of hydrogen peroxide generation by the action of glucose oxidase (GOx, EC 1.1.3.4) on glucose substrate. The resulting chemiluminescent signal is a long-lived glow. The magnitude of the chemiluminescent signal is directly proportional to the quantity of GOx present and has been used to measure GOx with a sensitivity of 1.8 x 10(-16) mol. In addition, this ability to monitor GOx activity has been utilized in an alkaline phosphatase (ALP, EC 3.1.3.1) amplification cascade assay. Here ALP catalyzes the formation of FAD from a prosthetogenic substrate FADP. FAD, a cofactor for a number of oxidase enzymes, then converts inactive apo-GOx to holo-GOx, the activity of which is monitored by the chemiluminescent endpoint and facilitates detection of ALP over the range 10(-15) to 4.1 x 10(-19) mol. The clinical utility of this system has been demonstrated by application to the assay of human thyrotrophin (TSH, sensitivity 0.005 mU/liter).

Acridines↗
PubMed1998

Measurement of the performance of air cleaners against the particulate element of rosin-based solder flux fume.

A number of commercially available air cleaners designed for use against solder fume have been examined. The fume capture efficiencies have been measured with a tracer gas comprising a neutrally buoyant mixture of sulphur hexafluoride and helium, and the filtration efficiencies have been measured using solder fume produced at a constant concentration, laboratory-generated monodisperse aerosols, and standard aerosols. The extractor volume flow rates of the simpler types of fume collection units, measured by us, differed from those reported by manufacturers. The capture efficiency of these units was good when the soldering iron was less than about 20 cm from the air intake, but the filtration efficiency against particulates and, therefore, the protection offered, was poor. More robust LEV units containing a HEPA filter had a similar capture efficiency, but a filtration efficiency that was well above the standard strictly necessary; such units will give good protection if properly used. The tip-extraction type of system was found to be very effective but the extraction nozzle rapidly became blocked with the rosin in the solder. Subsidiary measurements of vapour filtration efficiency were made. Activated carbon filters in the form of foams, used with the simpler type of cleaner, had negligible filtration efficiency against either particulates or vapours and would, therefore, offer no protection against any hazardous component of the fume. The granular carbon filter in the tip-extraction system was an effective vapour filter.

Aerosols↗
PubMed1998

Effects of high fat versus high carbohydrate diets on plasma lipids and lipoproteins in endurance athletes.

PURPOSE AND METHODS: Recent research suggesting the performance benefits of high fat diets for endurance athletes have been viewed with caution because of the potential negative health consequences, including increased coronary heart disease risk. This study examined the effects of a high fat (HF: 50% of total energy from fat, 37% carbohydrate) versus a high carbohydrate (HC: 15% of total energy from fat, 69% carbohydrate) diet on plasma lipids and lipoproteins in 32 endurance trained cyclists over a 3-month period. Plasma total, low density lipoprotein (LDL), high density lipoprotein (HDL), HDL2 and HDL3 cholesterol, triglycerides, apolipoprotein A1, and hematocrit (Hct) were measured at baseline and after weeks 4, 8, and 12. RESULTS: Changes in lipids and lipoproteins from baseline to week 12 did not differ between the two groups except for triglycerides, which increased significantly from 1.04 +/- 0.17 mmol.L-1 to 1.28 +/- 0.31 mmol.L-1 in HC (P = 0.012). The only significant changes that occurred within each group from baseline to week 12 was the significant increase in total cholesterol and triglycerides in HC. Body composition changes did not differ between the two groups from baseline to week 12 as measured by dual x-ray absorptiometry. CONCLUSIONS: During periods of endurance training when energy requirements are high, increasing the percentage of fat in the diet to approximately 50% of total energy did not result in adverse changes to the plasma lipoprotein profiles of this group of athletes.

Absorptiometry, Photon↗
PubMed1998

Nucellain, a barley homolog of the dicot vacuolar-processing protease, is localized in nucellar cell walls.

The nucellus is a complex maternal grain tissue that embeds and feeds the developing cereal endosperm and embryo. Differential screening of a barley (Hordeum vulgare) cDNA library from 5-d-old ovaries resulted in the isolation of two cDNA clones encoding nucellus-specific homologs of the vacuolar-processing enzyme of castor bean (Ricinus communis). Based on the sequence of these barley clones, which are called nucellains, a homolog from developing corn (Zea mays) grains was also identified. In dicots the vacuolar-processing enzyme is believed to be involved in the processing of vacuolar storage proteins. RNA-blot and in situ-hybridization analyses detected nucellain transcripts in autolysing nucellus parenchyma cells, in the nucellar projection, and in the nucellar epidermis. No nucellain transcripts were detected in the highly vacuolate endosperm or in the other maternal tissues of developing grains such as the testa or the pericarp. Using an antibody raised against castor bean vacuolar-processing protease, a single polypeptide was recognized in protein extracts from barley grains. Immunogold-labeling experiments with this antibody localized the nucellain epitope not in the vacuoles, but in the cell walls of all nucellar cell types. We propose that nucellain plays a role in processing and/or turnover of cell wall proteins in developing cereal grains.

Amino Acid Sequence↗
PubMed1998

Chemokine coreceptor usage by diverse primary isolates of human immunodeficiency virus type 1.

We tested chemokine receptor subset usage by diverse, well-characterized primary viruses isolated from peripheral blood by monitoring viral replication with CCR1, CCR2b, CCR3, CCR5, and CXCR4 U87MG.CD4 transformed cell lines and STRL33/BONZO/TYMSTR and GPR15/BOB HOS.CD4 transformed cell lines. Primary viruses were isolated from 79 men with confirmed human immunodeficiency virus type 1 (HIV-1) infection from the Chicago component of the Multicenter AIDS Cohort Study at interval time points. Thirty-five additional well-characterized primary viruses representing HIV-1 group M subtypes A, B, C, D, and E and group O and three primary simian immunodeficiency virus (SIV) isolates were also used for these studies. The restricted use of the CCR5 chemokine receptor for viral entry was associated with infection by a virus having a non-syncytium-inducing phenotype and correlated with a reduced rate of disease progression and a prolonged disease-free interval. Conversely, broadening chemokine receptor usage from CCR5 to both CCR5 and CXCR4 was associated with infection by a virus having a syncytium-inducing phenotype and correlated with a faster rate of CD4 T-cell decline and progression of disease. We also observed a greater tendency for infection with a virus having a syncytium-inducing phenotype in men heterozygous for the defective CCR5 Delta32 allele (25%) than in those men homozygous for the wild-type CCR5 allele (6%) (P = 0.03). The propensity for infection with a virus having a syncytium-inducing phenotype provides a partial explanation for the rapid disease progression among some men heterozygous for the defective CCR5 Delta32 allele. Furthermore, we did not identify any primary viruses that used CCR3 as an entry cofactor, despite this CC chemokine receptor being expressed on the cell surface at a level commensurate with or higher than that observed for primary peripheral blood mononuclear cells. Whereas isolates of primary viruses of SIV also used STRL33/BONZO/TYMSTR and GPR15/BOB, no primary isolates of HIV-1 used these particular chemokine receptor-like orphan molecules as entry cofactors, suggesting a limited contribution of these other chemokine receptors to viral evolution. Thus, despite the number of chemokine receptors implicated in viral entry, CCR5 and CXCR4 are likely to be the physiologically relevant chemokine receptors used as entry cofactors in vivo by diverse strains of primary viruses isolated from blood.

Animals↗
PubMed1998

Getting a validated guideline into local practice: implementation and audit of the SIGN guideline on the prevention of deep vein thrombosis in a district general hospital.

This paper describes the implementation of a specific clinical guideline on venous thromboprophylaxis and outlines the audit design and methods used to achieve this objective. A member of the clinical staff was seconded to oversee this implementation and co-ordinate audit of current in the main clinical specialties within the trust. The Trust Clinical Audit Committee agreed to fund this low cost initiative (approximately 3,800 pounds) from clinical guideline monies. Findings from the initial audit revealed a total of 224 patients identified as 'at risk' of developing deep vein thrombosis or pulmonary embolism. Of this number 72.8%, (n = 163), were prescribed prophylaxis compared with the pre-set standard of 90.0%. Fifty four percent, (n = 122), of all identified patients were prescribed the correct prophylaxis in accordance with SIGN guideline recommendations. As a result of the initial findings local prevention protocols were developed or upgraded as required in line with the national guideline. The repeat audit findings highlighted a significant increase in the number of 'at risk' patients prescribed prophylaxis rising from 72.8% to 97.4% (P < 0.001) and similarly from 54.5% to 95.9% for those prescribed the correct prophylaxis (P < 0.001).

Hospitals, General↗
PubMed1998

Opioid-induced analgesia in neonatal dogs: pharmacodynamic differences between morphine and fentanyl.

Whether the analgesic effects of opioids change as a neonate matures is not well understood. To address this issue, we determined the pharmacokinetics and pharmacodynamics of analgesic effects of morphine and fentanyl in 35 dogs aged 1 to 34 days. Opioids were infused to produce analgesia, response times to a noxious thermal stimulus were measured and plasma opioid concentrations were determined. An effect compartment pharmacodynamic model was fit to the values for time to response to determine the rate constant for equilibration (Keo) between plasma and effect-site (Ce) concentrations and analgesic effect (increase in time to response to a noxious stimulus) above baseline per microgram/ml of Ce (delta). A time-to-event data analysis (modeled with a Weibull function) was used to account for censored time to response values. For both opioids, values for Keo did not vary with age. Values for delta decreased with age (i.e., decreasing sensitivity with increasing age), and the magnitude of the change during the first month of life was similar for the two opioids. In the context of our previous study concerning ventilatory depressant effects of these opioids (that sensitivity to morphine, but not to fentanyl, decreased markedly during the first month of life), these results in dogs suggest that fentanyl has greater utility than morphine in neonates during spontaneous ventilation.

Analgesia↗
PubMed1997

Characterization of a subset of the basic-helix-loop-helix-PAS superfamily that interacts with components of the dioxin signaling pathway.

In an effort to better understand the mechanism of toxicity of 2,3,7, 8-tetrachlorodibenzo-p-dioxin, we employed an iterative search of human expressed sequence tags to identify novel basic-helix-loop-helix-PAS (bHLH-PAS) proteins that interact with either the Ah receptor (AHR) or the Ah receptor nuclear translocator (ARNT). We characterized five new "members of the PAS superfamily," or MOPs 1-5, that are similar in size and structural organization to the AHR and ARNT. MOPs 1-4 have N-terminal bHLH and PAS domains and C-terminal variable regions. MOP5 contained the characteristic PAS domain and a variable C terminus; it is possible that the cDNA contains a bHLH domain, but the entire open reading frame has yet to be completed. Coimmunoprecipitation studies, yeast two-hybrid analysis, and transient transfection experiments demonstrated that MOP1 and MOP2 dimerize with ARNT and that these complexes are transcriptionally active at defined DNA enhancer sequences in vivo. MOP3 was found to associate with the AHR in vitro but not in vivo. This observation, coupled with the fact that MOP3 formed tighter associations with the 90-kDa heat shock protein than the human AHR, suggests that MOP3 may be a conditionally active bHLH-PAS protein that requires activation by an unknown ligand. The expression profiles of the AHR, MOP1, and MOP2 mRNAs, coupled with the observation that they all share ARNT as a common dimeric partner, suggests that the cellular pathways mediated by MOP1 and MOP2 may influence or respond to the dioxin signaling pathway.

Amino Acid Sequence↗
PubMed1997

Cell wall (1-->3)- and (1-->3, 1-->4)-beta-glucans during early grain development in rice (Oryza sativa L.).

Immunogold labeling was used to study the distribution of (1-->3)-beta-glucans and (1-->3, 1-->4)-beta-glucans in the rice grain during cellularization of the endosperm. At approximately 3-5 d after pollination the syncytial endosperm is converted into a cellular tissue by three developmentally distinct types of wall. The initial free-growing anticlinal walls, which compartmentalize the syncytium into open-ended alveoli, are formed in the absence of mitosis and phragmoplasts. This stage is followed by unidirectional (centripetal) growth of the anticlinal walls mediated by adventitious phragmoplasts that form between adjacent interphase nuclei. Finally, the periclinal walls that divide the alveoli are formed in association with centripetally expanding interzonal phragmoplasts following karyokinesis. The second and third types of wall are formed alternately until the endosperm is cellular throughout. All three types of wall that cellularize the endosperm contain (1-->3)-beta-glucans but not (1-->3, 1-->4)-beta-glucans, whereas cell walls in the surrounding maternal tissues contain considerable amounts of (1-->3, 1-->4)-beta-glucans with (1-->3)-beta-glucans present only around plasmodesmata. The callosic endosperm walls remain thin and cell plate-like throughout the cellularization process, appearing to exhibit a prolonged juvenile state.

Cell Wall↗
PubMed1997

The construction and validation of a high containment nose-only rodent inhalation facility.

A new nose-only inhalation facility for rodents has been designed and built for operation within a high containment glove box facility. All operations using the equipment, whether concerned with aerosol generation or animal handling and exposure are conducted under high containment with total operator protection. The facility has been used to investigate known carcinogenic fibres such as the amphiboles. It has been designed to be resistant to most chemicals, under the conditions of an experiment, and can be used with radioactive material within the limitations which would be imposed for radiological protection. This paper describes the construction and validation of the equipment using titanium dioxide.

Administration, Inhalation↗
PubMed1997

A randomized trial of two vacuum extraction techniques.

OBJECTIVE: To determine whether two techniques of vacuum extraction delivery-continuous vacuum and intermittent vacuum-have different effects on maternal-fetal outcomes. METHODS: Patients to be delivered by vacuum extraction were randomized to receive continuous or intermittent vacuum. All deliveries were performed using the M-cup. In the continuous group, the level of vacuum was brought to 600 mmHg between contractions and was maintained at that level until delivery of the infant. Active efforts were made to prevent fetal loss-of-station between contractions by maintaining traction. In the intermittent group, the level of vacuum was decreased to 100 mmHg between contractions and no effort was made to prevent fetal loss-of-station. RESULTS: A total of 322 patients were randomized: 164 in the continuous arm and 158 in the intermittent group. The continuous method did not effect delivery faster (continuous 167 +/- 175 seconds versus intermittent 167 +/- 150 seconds; P = .97), nor did it lead to a reduction in method failures (continuous 12, intermittent nine; P = .72). The intermittent method did not appear to offer any benefit to the neonate regarding cephalhematoma formation (continuous 20, intermittent 17; P = .686) or any other measure of neonatal outcome. Maternal lacerations and episiotomy extensions were evenly distributed between the groups. Overall, the efficacy rate of the vacuum cup was 93.5% and the cephalhematoma rate was 11.5%. CONCLUSION: No differences in maternal or fetal outcome could be demonstrated if the level of vacuum was decreased between contractions or if an effort was made to prevent fetal loss-of-station. The clinical results obtained in this trial using the M-cup are similar to the published results with the stainless-steel Malmstrom cup.

Adult↗